For a nervous system to be properly wired up, the axons have to be guided toward the correct targets and the dendrites need to have the correct branching pattern and structural specialization. Despite considerable progresses that have been made recently, we still know relatively little about the molecular mechanisms that control dendrite development as compared to those controlling axon guidance. We hypothesize that a systematic screen for dendrite mutants in a model system is likely to provide a comprehensive means of identifying those molecular mechanisms. Once the molecular basis is characterized, it will be possible to test for its general applicability in other animals. For this purpose, we have developed the multiple dendritic (MD) neurons of the Drosophila peripheral nervous system (PNS) as a model system. We have been using this model system to perform a genetic dissection of dendrite development by identifying, cloning and studying genes of interest in order to uncover the core programs that control dendrite morphogenesis. Our ongoing study has begun to yield important insights about the molecular basis of dendrite development in Drosophila. Our studies have helped to formulate important questions that have only begun to be addressed. For this proposal, we will focus on three areas: the differential regulation of dendrite and axon growth; the molecular mechanisms that control dendritic self-avoidance and tiling and the molecular machinery used to maintain dendritic arbors. Given the striking conservation of many molecular mechanisms that control various developmental processes including axon guidance, it is highly likely that many of the molecular mechanisms controlling dendrite development are conserved between Drosophila and mammals. Indeed, we have already had considerable success in our ongoing efforts to extend our findings from Drosophila to mammalian brain. Since dendrite defects have been implicated in certain human mental disorders such as autism, this work will contribute to the understanding and eventual treatment of human neurological diseases many of which have pathology in dendrites. PUBLIC HEALTH RELEVANCE: This project aims to elucidate the molecular mechanisms that control dendrite development by using Drosophila sensory neurons as a model system. Given there is already strong evidence that many molecular mechanisms that control dendrite development are evolutionarily conserved, this work is likely to contribute to the understanding and eventual treatment of human neurological disorders, many of which have pathology in dendrites.